In rats receiving repeated injections of imipramine, there is a reduction in the number of high affinity binding sites for (3H) imipramine and (3H) dihydroalprenolol present in crude synaptic membrane preparations from various brain structures. The location of the sites that become subsensitive to the two ligands did not coincide; the binding sites to (3H) imipramine became subsensitive in the hippocampus but not in cortex of cerebellum. In contrast the binding sites to (3H) dihydroalprenolol became subsensitive in cortex and cerebellum but not in hippocampus. It can be suggested that in rats repeatedly treated with imipramine the down regulation of beta-adrenergic receptors does not depend on the down regulation of the high affinity binding sites for imipramine. Such a dissociation is supported further by experiments with rats treated with iprindol.